title: Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients.
abstract: BACKGROUND
  Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients.
  
  
  METHODS
  Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival.
  
  
  RESULTS
  Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04], whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively).
  
  
  CONCLUSIONS
  In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.
authors.affiliation: Department of Anesthesiology, Division of Critical Care, Vanderbilt University School of Medicine, 526 MAB, 1211 21st Ave South, Nashville, TN 37212, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: McGrane
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Girard
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Thompson
authors.forename: Ayumi K
authors.initials: AK
authors.lastname: Shintani
authors.forename: Alison
authors.initials: A
authors.lastname: Woodworth
authors.forename: E Wesley
authors.initials: EW
authors.lastname: Ely
authors.forename: Pratik P
authors.initials: PP
authors.lastname: Pandharipande
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D016638:Critical Illness; D003693:Delirium / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012121:Respiration, Artificial; D013997:Time Factors
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide